Rabeprazole sodium is a proton pump inhibitor which can produce profound and sustained inhibition of gastric acid secretion with responses of Proton pump inhibitors being more rapid when compared with other anti-secretory drugs. Proton pump inhibitors work by inhibiting the production of stomach acid, by shutting down a system in the stomach known as proton pump (Hydrogen-Potassium adenosine triphosphate enzyme system).
EP0268956 A2 and WO01/04109 have disclosed the preparation of rabeprazol sodium. It describes the synthesis of rabeprazole sulphide, rabeprazole base and its sodium salt. Rabeprazole sulphide (2-[{4-(3-methoxy propoxy)-3-methyl pyridine-2-yl}methyl thio]-1H-benzimidazole) is prepared by condensation of 2-chloromethyl-4-[3-methoxy propoxy]-3-methylpyridine and 2-mercapto benzimidazole in ethanol by using sodium hydroxide. This mixture is stirred at 50° C. for 3 hours. The solvent is distilled to obtain residue which is further purified by column chromatography using silica gel.
Rabeprazole is prepared by oxidizing 2-[{4-(3-methoxy propoxy)-3-methyl pyridine-2-yl}methyl thio]-1H-benzimidazole with m-Chloroperbenzoic acid to afford the Rabeprazole base which is further converted to its sodium salt by using 0.1 N aqueous solution of Sodium hydroxide, followed by addition of ethanol. The water is removed by azeotropic distillation and the product is precipitated by using ether as solvent. The disadvantage of this process is the presence of higher residual solvent content in the product resulting in lower potency. This method is not suitable for industrial scale preparation of rabeprazole sodium.
WO 02/062786 discloses a process for preparation of Rabeprazole substantially free of a sulphone by-product wherein the oxidation is carried out using tertiary butyl hydroperoxide in the presence of vanadyl bis-acetyl acetonate catalyst.
PCT Application PCT/GB2004/000064 and International Publication Number WO 2004/063188 A1, discloses the preparation of rabeprazole and benzimidazole type of compounds. Accordingly, rabeprazole base is prepared by oxidation using sodium hypohalites and isolated. Rabeprazole sodium is prepared by dissolving rabeprazole base in ethylacetate and methanolic ammonia mixture to which methanolic sodium hydroxide is added. The solvent is distilled and rabeprazole sodium is isolated from ethylacetate and n-heptane/n-hexane mixture.
These prior art processes cited above have many disadvantages and are not ideally suited for industrial application. These processes involve use of expensive solvent and hazardous oxidizing reagents. Further the isolation procedure described in the prior art involves azeotropic distillation of water during which the product is exposed to high temperature and leads to certain impurities.
The related prior art process also involves use ether which is not suited for large scale production. Further, purification of the final product in prior art is done by column chromatography which also is a not an industrially viable process.
Further the conversion of rabeprazole base to its sodium salt is a multiple step process, which involves isolation, purification and drying of the intermediates used.